The overall objective of the entire project is to study by what mechanism the immunogenicity of organ allografts may be reduced by graft pretreatment - thereby permitting survival of allogenic organ grafts. The seminal observation here is that mongrel dog kidneys perfused with Concanavalin A (Con A) in vitro and transplanted into allogenic dogs who received minimal immunosuppression, survived for prolonged periods of time. The original grant was designed to : 1) Study the possible mechanisms by which Con A bound to organ grafts can lead to prolongation in allogenic recipients. 2) Determine the optimal conditions of the treatment of organ allografts which will permit prolonged allograft survival. 3) Investigate how Con A and other modifiers of immunogenicity can alter the immunogenicity of grafts utilizing the mixed lymphocyte culture to simulate immunologic stimulation. 4) Apply the lessons learned in the kidney allograft system to organ allografts of liver, intestine, heart and pancreas. 5) Determine the effects on the immunogenicity of organ and tissue allografts of other substances which can be used to pretreat the graft iteself. The goals in 1977-78 were to (a) further study the distribution of Con A after kidney perfusion in order to determine the mechanism of action, (b) pursue other models simpler and cheaper than the dog, and (c) pursue the mechanism by which graft pretreatment alters host response.